Miniscrews for orthodontic anchorage: analysis of risk factors correlated with the progressive susceptibility to failure.

INTRODUCTION: The phenomenon of orthodontic anchorage miniscrews loosening after being implanted several times happens in daily clinical practice, and the reasons need to be traced. This study aimed to investigate the underlying risk factors influencing the progressive susceptibility of orthodontic miniscrews to failure. METHODS: Overall, 889 miniscrews were successively inserted into 347 patients because some loosened or fell off once, twice, or more before achieving their purposes. The number of miniscrew failures (ie, once, twice, or more) was defined as progressive susceptibility to failure. The clinical indicators were assessed via univariate analysis, multicollinearity diagnosis, and Poisson log-linear regression model with stepwise calculation to screen out. RESULTS: The progressive susceptibility of miniscrews to failure was proved to be affected by the age of patients, the onset of force application, site of placement, and appliance type. Age and onset of force application presented a negative relationship with susceptibility. Miniscrews inserted in the palatal region appeared to be more stable than the forepart of the arch. In contrast, the retromaxillary and retromandibular areas obtained the lowest stability. The patients with fixed appliances were more unlikely to suffer progressive failure than removable appliances. In addition, the larger number of screws inserted in each patient, the greater probability of failure. CONCLUSIONS: Younger people with removable appliances that miniscrews inserted in the retromaxillary or retromandibular regions and earlier onsets of loading had a higher progressive susceptibility to loosening. Meanwhile, the failure rate was elevated with the increasing number of screws per patient received.

Appointment impact and orthodontic emergency occurrence during the coronavirus disease 2019 pandemic: A retrospective study.

INTRODUCTION: This retrospective study aimed to quantify the impact of coronavirus disease 2019 (COVID-19) on the orthodontic appointment and make an analysis of orthodontic emergencies (OEs) that occurred during the pandemic. METHODS: A total of 628 patients were randomly sampled from 3489 subjects who were undergoing active orthodontic treatment with fixed appliances, and the medical records were reviewed. OE occurrence was analyzed from 617 patients who had explicit return-visit records after the COVID-19 outbreak. Wilcoxon signed rank tests, chi-square tests, and a binary logistic regression were performed. RESULTS: The return-visit of 98.6% of the patients was delayed significantly with an increase over 8.98 ± 4.76 weeks (P <0.001). In general, 32.3% of the patients suffered from various OEs while waiting for their first return-visit, and bracket or band debonding was the most frequently reported category. Most OEs did not receive timely treatments because of the lockdown. The incidence was nearly 2 times higher than that of the normal appointment times. No correlation was found between OE occurrence and different demographic and clinical characteristics of patients. The therapeutic progress of patients, especially those in stage 3, was postponed because of the occurrence of OEs. CONCLUSIONS: Regardless of the limitations, our study suggested that it is highly possible that the COVID-19 pandemic has delayed appointments of fixed orthodontic patients. OEs did bother a minority of patients and could not be settled in time during the lockdown, which had a negative impact on the near-term treatment progress and should have been prevented. Further studies are required to investigate the long-dated influence of COVID-19 on orthodontic practices.

A Janus, robust, biodegradable bacterial cellulose/Ti3C2Tx MXene bilayer membranes for guided bone regeneration.

Guided bone regeneration (GBR) stands as an essential modality for craniomaxillofacial bone defect repair, yet challenges like mechanical weakness, inappropriate degradability, limited bioactivity, and intricate manufacturing of GBR membranes hindered the clinical efficacy. Herein, we developed a Janus bacterial cellulose(BC)/MXene membrane through a facile vacuum filtration and etching strategy. This Janus membrane displayed an asymmetric bilayer structure with interfacial compatibility, where the dense layer impeded cell invasion and the porous layer maintained stable space for osteogenesis. Incorporating BC with Ti3C2Tx MXene significantly enhanced the mechanical robustness and flexibility of the material, enabling clinical operability and lasting GBR membrane supports. It also contributed to a suitable biodegradation rate, which aligned with the long-term bone repair period. After demonstrating the desirable biocompatibility, barrier role, and osteogenic capability in vitro, the membrane's regenerative potential was also confirmed in a rat cranial defect model. The excellent bone repair performance could be attributed to the osteogenic capability of MXene nanosheets, the morphological cues of the porous layer, as well as the long-lasting, stable regeneration space provided by the GBR membrane. Thus, our work presented a facile, robust, long-lasting, and biodegradable BC/MXene GBR membrane, offering a practical solution to craniomaxillofacial bone defect repair.

Circ_0036490 and DKK1 competitively bind miR-29a to promote lipopolysaccharides-induced human gingival fibroblasts injury.

MicroRNA (miRNA) plays a regulatory role in periodontitis. This study aimed to explore whether miR-29a could affect lipopolysaccharides (LPSs)-induced injury in human gingival fibroblasts (HGFs) through the competitive endogenous RNAs (ceRNA) mechanism. Periodontal ligament (PDL) tissues and HGFs were derived from patients with periodontitis and healthy volunteers. Periodontitis cell model was established by treating HGFs with LPS. Expression levels of circ_0036490, miR-29a, and DKK1 were evaluated by the reverse transcription quantitative real-time PCR (RT-qPCR) method. Western blotting assay was performed to assess protein expression levels of pyroptosis-related proteins and Wnt signalling related proteins. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Concentration of lactate dehydrogenase (LDH), interleukin (IL)-1ß, and IL-18 were determined by Enzyme-linked immunosorbent assay (ELISA). Pyroptosis rate were determined by flow cytometry assay to evaluate pyroptosis. The interaction between miR-29a and circ_0036490 or DKK1 was verified by dual-luciferase reporter and RNA pull-down assays. MiR-29a expression was lower in PDL tissues of patients with periodontitis than that in healthy group; likewise, miR-29a was also downregulated in LPS-treated HGFs. Overexpression of miR-29a increased cell viability and decreased pyroptosis of HGFs induced by LPS while inhibition of miR-29a exerted the opposite role. MiR-29a binds to circ_0036490 and elevation of circ_0036490 contributed to dysfuntion of LPS-treated HGFs and reversed the protection function of elevated miR-29a. In addition, miR-29a targets DKK1. Overexpression of DKK1 abrogated the effects of overexpressed miR-29a on cell vaibility, pyroptosis, and protein levels of Wnt signalling pathway of LPS-treated HGFs. Circ_0036490 and DKK1 competitively bind miR-29a to promote LPS-induced HGF injury in vitro. Wnt pathway inactivated by LPS was activated by miR-29a. Thence, miR-29a may be a promising target for periodontitis.

Invisalign Treatment of a Three-Year-Old Child with Bilateral Posterior Scissor Bite and Multisite Upper Airway Obstruction: A Case Report.

BACKGROUND: Scissor bites have been reported in relatively few epidemiological studies because of their extremely low prevalence rate (below 1%). The etiology of scissor bites remains obscure, but its impact on growth and function should not be ignored. METHODS: In this case report, a novel treatment that utilizes Invisalign aligners was performed on a 3-year-old child who presented with a bilateral posterior scissor bite and anterior crossbite, accompanied by multisite obstruction in the upper airway. The aligners functioned as occlusion pads to unlock the scissor bite relationship and combined with cross-traction to narrow the maxillary arch and enlarge the mandibular arch simultaneously. RESULTS: The duration of orthodontic therapy was 28 weeks. A multidisciplinary consultation (orthodontics department, ENT department, and spinal surgery) was conducted and a stable result was achieved. A healthy occlusal relationship, improved dental esthetics and a better lateral profile were eventually obtained. CONCLUSIONS: Positive treatment outcomes rely on patients' good compliance in this case. In addition, we hope that clinicians will consider our situation in terms of alternative treatments and interprofessional experience.

A Ti3C2 MXene-integrated near-infrared-responsive multifunctional porous scaffold for infected bone defect repair.

Infected bone defect repair has long been a major challenge in orthopedic surgery. Apart from bacterial contamination, excessive generation of reactive oxygen species (ROS), and lack of osteogenesis ability also threaten the defect repair process. However, few strategies have been proposed to address these issues simultaneously. Herein, we designed and fabricated a near-infrared (NIR)-responsive, hierarchically porous scaffold to address these limitations in a synergetic manner. In this design, polymethyl methacrylate (PMMA) and polyethyleneimine (PEI) were used to fabricate the porous PMMA/PEI scaffolds via the anti-solvent vapor-induced phase separation (VIPS) process. Then, Ti3C2 MXenes were anchored on the scaffolds through the dopamine-assisted co-deposition process to obtain the PMMA/PEI/polydopamine (PDA)/MXene scaffolds. Under NIR laser irradiation, the scaffolds were able to kill bacteria through the direct contact-killing and synergetic photothermal effect of Ti3C2 MXenes and PDA. Moreover, MXenes and PDA also endowed the scaffolds with excellent ROS-scavenging capacity and satisfying osteogenesis ability. Our experimental results also confirmed that the PMMA/PEI/PDA/MXene scaffolds significantly promoted new bone formation in an infected mandibular defect model. We believe that our study provides new insights into the treatment of infected bone defects.

Clear aligner treatment for a four-year-old patient with anterior cross-bite and facial asymmetry: A case report.

BACKGROUND: Clear aligners have been widely used to treat malocclusions from crowding, extraction cases to orthodontic-orthognathic cases, and practitioners are exploring the border of it. For the first time, clear aligners were used to early intervene anterior cross-bite and facial asymmetry. CASE SUMMARY: This case report described a four-year-old child presented with anterior cross-bite and facial asymmetry associated with functional mandibular shift, who had undergone a failed treatment with conventional appliances. The total treatment time was 18 weeks, and a stable outcome was obtained. CONCLUSION: The increasing need in early treatment highlights the need for clinicians to thoroughly investigate for the patient regarding clinical manifestation as well as patient compliance. We hope that our case will be contemplated by clinicians when seeking for treatment alternatives.

Identification of a novel missense mutation in non-syndromic familial multiple supernumerary teeth.

OBJECTIVE: This study intended to evaluate the involvement of genetic factors in the etiology of non-syndromic multiple supernumerary teeth. DESIGN: We filtered the single nucleotide polymorphisms (SNPs) of the proband and his mother with similar phenotypes through whole-genome sequencing (WGS). By integrating multiple databases related to human genome mutations and disease information for mutation annotation, we excluded the SNPs of people without supernumerary teeth. Subsequently, the bioinformatics analysis tools (Sorting Intolerant From Tolerant (SIFT) < 0.05, Polymorphism Phenotyping (PolyPhen) > 0.90) were used to screen out the most correlated SNPs of the disease, besides, Gene Ontology (GO) analysis (P<0.05, FDR<0.05) and Sanger sequencing was applied to further verify the candidate pathogenic mutation point. RESULTS: A novel heterozygous variant in fer-1 like family member 6 (FER1L6) gene likely denoted pathogenicity in non-syndromic familial multiple supernumerary teeth. We identified a cohort of 3499 non-synonymous SNPs (nsSNPs), and only 142 nsSNPs with the score of SIFT < 0.05 and PolyPhen > 0.90 were retained. Then we got 54 nsSNPs from 31 candidate genes through GO analysis. Sanger sequencing revealed a missense variant in exon 31 of the FER1L6 gene, causing a transition from guanine to adenine in position 1447 of protein kinase C conserved region 2. CONCLUSIONS: We identified a novel heterozygous chromosome 8q24.13 mutation of FER1L6, which was a new mutation site identified in non-syndromic familial multiple supernumerary teeth through genetic analysis of a Chinese family.

Three-dimensional, biomimetic electrospun scaffolds reinforced with carbon nanotubes for temporomandibular joint disc regeneration.

Temporomandibular disorder (TMD) remained a huge clinical challenge, with high prevalence but limited, unstable, and only palliative therapeutic methods available. As one of the most vulnerable sites implicated in TMD, the temporomandibular joint disc (TMJD) displayed a complicated microstructure, region-specific fibrocartilaginous distribution, and poor regenerative property, which all further hindered its functional regeneration. To address the problem, with versatile and relatively simple electrospinning (ELS) technique, our study successfully fabricated a biomimetic, three-dimensional poly (ϵ-caprolactone) (PCL)/polylactide (PLA)/carbon nanotubes (CNTs) disc scaffold, whose biconcave gross anatomy and regionally anisotropic microstructure recapitulating those of the native disc. As in vitro results validated the superior mechanical, bioactive, and regenerative properties of the biomimetic scaffolds with optimal CNTs reinforcement, we further performed in vivo experiments. After verifying its biocompatibility and ectopic fibrochondrogenicity in nude mice subcutaneous implantation models, the scaffolds guided disc regeneration and subchondral bone protection were also confirmed orthotopically in rabbits TMJD defected areas, implying the pivotal role of morphological cues in contact-guided tissue regeneration. In conclusion, our work represents a significant advancement in complex, inhomogeneous tissue engineering, providing promising clinical solutions to intractable TMD ailments. STATEMENT OF SIGNIFICANCE: Complex tissue regeneration remains a huge scientific and clinical challenge. Although frequently implicated in temporomandibular joint disorder (TMD), functional regeneration of injured temporomandibular joint disc (TMJD) is extremely hard to achieve, mainly because of the complex anatomy and microstructure with regionally variant, anisotropic fiber alignments in the native disc. In this study, we developed the biomimetic electrospun scaffold with optimal CNTs reinforcement and regionally anisotropic fiber orientations. The excellent mechanical and bioactive properties were confirmed both in vitro and in vivo, effectively promoting defected discs regeneration in rabbits. Besides demonstrating the crucial role of morphological biomimicry in tissue engineering, our work also presents a feasible clinical solution for complex tissue regeneration.

Effect of placement angle on the stability of loaded titanium microscrews: a microcomputed tomographic and biomechanical analysis.

INTRODUCTION: The aim of this study was to evaluate the impact of the placement angle on the stability of loaded microscrews. METHODS: Forty-eight microscrews were placed at 4 angles ( 30°, 50°, 70°, and 90°) into the tibiae of 12 beagles, loaded with a force of 2 N immediately, and maintained for 8 weeks. Microcomputed tomography and pullout tests were used for morphometric and biomechanical analyses, respectively. RESULTS: All microcomputed tomography parameters and the peak loads at extraction of the microscrews were influenced by the placement angles of the microscrews. The higher microcomputed tomography parameters and the peak load at extraction were measured at angles from 50° to 70°. Oblique and vertical placement angles resulted in reduced stability of the loaded microscrews (P <0.05). CONCLUSIONS: To achieve the best stability of microscrews, a placement angle of 50° to 70° is advisable.

Carbon Nanotube Reinforced Collagen/Hydroxyapatite Scaffolds Improve Bone Tissue Formation In Vitro and In Vivo.

Current bone regeneration strategies faced major challenges in fabricating the bionic scaffolds with nano-structure, constituents and mechanical features of native bone. In this study, we developed a new porous scaffold by adding the multi-walled carbon nanotube (MWCNT) into collagen (Col)/hydroxyapatite (HA) composites. Data showed that 0.5%CNT/Col/HA (0.5%CNT) group was approximately tenfolds stiffer than Col-HA, and it was superior in promoting bone marrow mesenchymal stem proliferation and spreading, mRNA and protein expressions of bone sialoprotein (BSP) and osteocalcin (OCN) than Col-HA group. Moreover, we utilized 0.5%CNT composite to repair the rat calvarial defects (8 mm diameter) in vivo, and observed the new bone formation by 3D reconstruction of micro CT, HE and Masson staining, and BSP, OCN by immunohistochemical analysis. Results showed that newly formed bone in 0.5%CNT group was significantly higher than that in Col-HA group at 12 weeks. These findings highlighted a promising strategy in healing of large area bone defect with MWCNT added into the Col-HA scaffold as they possessed the combined effects of mechanical strength and osteogenicity.

Factors Affecting the Clinical Success Rate of Miniscrew Implants for Orthodontic Treatment.

PURPOSE: The purpose of this study was to evaluate the various factors that influence the success rate of miniscrew implants used as orthodontic anchorage. MATERIALS AND METHODS: Potential confounding variables examined were sex, age, vertical (FMA) and sagittal (ANB) skeletal facial pattern, site of placement (labial and buccal, palatal, and retromandibular triangle), arch of placement (maxilla and mandible), placement soft tissue type, oral hygiene, diameter and length of miniscrew implants, insertion method (predrilled or drill-free), angle of placement, onset and strength of force application, and clinical purpose. The correlations between success rate and overall variables were investigated by logistic regression analysis, and the effect of each variable on the success rate was utilized by variance analysis. RESULTS: One hundred fourteen patients were included with a total of 253 miniscrew implants. The overall success rate was 88.54% with an average loading period of 9.5 months in successful cases. Age, oral hygiene, vertical skeletal facial pattern (FMA), and general placement sites (maxillary and mandibular) presented significant differences in success rates both by logistic regression analysis and variance analysis (P < .05). CONCLUSION: To minimize the failure of miniscrew implants, proper oral hygiene instruction and effective supervision should be given for patients, especially young (< 12 years) high-angle patients with miniscrew implants placed in the mandible.

Incorporation of aligned PCL-PEG nanofibers into porous chitosan scaffolds improved the orientation of collagen fibers in regenerated periodontium.

The periodontal ligament (PDL) is a group of highly aligned and organized connective tissue fibers that intervenes between the root surface and the alveolar bone. The unique architecture is essential for the specific physiological functionalities of periodontium. The regeneration of periodontium has been extensively studied by researchers, but very few of them pay attention to the alignment of PDL fibers as well as its functionalities. In this study, we fabricated a three-dimensional multilayered scaffold by embedding highly aligned biodegradable poly (ε-caprolactone)-poly(ethylene glycol) (PCE) copolymer electrospun nanofibrous mats into porous chitosan (CHI) to provide topographic cues and guide the oriented regeneration of periodontal tissue. In vitro, compared with random group and porous control, aligned nanofibers embedded scaffold could guide oriented arrangement and elongation of cells with promoted infiltration, viability and increased periodontal ligament-related genes expression. In vivo, aligned nanofibers embedded scaffold showed more organized arrangement of regenerated PDL nearly perpendicular against the root surface with more extensive formation of mature collagen fibers than random group and porous control. Moreover, higher expression level of periostin and more significant formation of tooth-supporting mineralized tissue were presented in the regenerated periodontium of aligned scaffold group. Incorporation of aligned PCE nanofibers into porous CHI proved to be applicable for oriented regeneration of periodontium, which might be further utilized in regeneration of a wide variety of human tissues with a specialized direction. STATEMENT OF SIGNIFICANCE: The regeneration of periodontium has been extensively studied by researchers, but very few of them give attention to the alignment of periodontal ligament (PDL) fibers as well as its functionalities. The key issue is to provide guidance to the orientation of cells with aligned arrangement of collagen fibers perpendicular against the root surface. This study aimed to promote oriented regeneration of periodontium by structural mimicking of scaffolds. The in vitro and in vivo performances of the scaffolds were further evaluated to test the topographic-guiding and periodontium healing potentials. We also think our research may provide ideas in regeneration of a wide variety of human tissues with a specialized direction.

Orthodontic mini-implant stability under continuous or intermittent loading: a histomorphometric and biomechanical analysis.

BACKGROUND: Both continuous and intermittent loadings are commonly applied in orthodontics. Clinical experiences and some studies believed that longer duration of force produce more effect (tooth movement, suture expansion, bone remodeling) than transient forces applied with the same magnitude. Alternatively, others indicated that interruption or recovery periods of various periods between loadings cause more bone remodeling and less root resorption. Therefore, which force is more favorable for osseointegration and stability of orthodontic mini-implant remains to be elucidated. PURPOSE: To evaluate the influence of continuous or intermittent loading on stability of titanium mini-implants. MATERIALS AND METHODS: One hundred ninety-two mini-implants were implanted bilaterally in intraradicular zones of mandibular M1 and P2 in 48 beagles. Loadings were delivered consecutively in continuous group, pauses were given for the last 3 or 7 days of each 2-week reactivation period for intermittent group A and B, respectively. The group unloaded was set as control. After 2, 4, 6 and 8 weeks, the animals were sacrificed and microscopic computerized tomography (µCT), histomorphological observation and pull-out test were applied. RESULTS: The µCT parameters of mini-implants in four groups were gradually increased with loading time prolonged, while the value of peak load at extraction (F(max)) increased and reached summit at week 6, but dropped slightly at week 8. In continuous group, all measurements were lower than those in intermittent groups at all time points (p < .05), and all values in intermittent group B were higher than those in intermittent group A. Histomorphology observation revealed different degrees of bone remodeling with new bone formation in the peri-implants region in different groups. CONCLUSIONS: Intermittent loading regimen is more favorable for obtaining stability than continuous force.

Histomorphometric and biomechanical analyses of the osseointegration of loaded orthodontic microscrews inserted at different cortical bone thickness sites.

OBJECTIVES: The aim of this study was to evaluate the osseointegration of loaded orthodontic microscrews at different cortical bone thickness (CBT) sites. STUDY DESIGN: Forty-eight microscrews were inserted bilaterally in the tibias of 12 beagles, and divided into thick and thin CBT group. After 1, 3, 5, and 7 weeks, the dogs were killed and bone-screw specimens prepared for polyfluorochrome sequential labeling, microscopic computerized tomography (µCT) analysis, and biomechanical pull-out testing. RESULTS: All µCT parameters were increased in the thin CBT group, and decreased in the thick CBT group with time passed. Fmax of microscrews in thick CBT sites reached a peak in week 1, but dropped to lowest levels in week 3. Remodeling, apposition, and measured deposition areas of 3 labels were significantly higher in the thin CBT group than in the thick CBT group (P < .05). CONCLUSIONS: Relatively larger CBT is of benefit for primary stability at early time points, whereas thinner CBT is more appropriate for achieving long-term stability with prolonged time.

Microcomputed tomographic and biomechanical analysis of orthodontic microscrew stability under continuous or intermittent force.

PURPOSE: To evaluate and compare the influence of continuous and intermittent forces on stability of titanium microscrews. MATERIALS AND METHODS: One hundred forty-four microscrews were inserted bilaterally in the intraradicular zones of the maxillary first molar and second premolar in 36 beagles. Loads were delivered consecutively in the continuous group (n = 12), in cycles of 12 hours on/paused for 12 hours in intermittent group A (n = 12), and in cycles of 24 hours on/paused for 24 hours in intermittent group B (n = 12). The on/off cycles were repeated for 1, 3, 5, or 7 weeks, after which the animals were sacrificed, and microcomputed tomography (micro-CT) and pull-out testing were performed. RESULTS: The micro-CT parameters of the microscrews in all three groups increased gradually with loading time. The value of peak load at extraction (Fmax) increased and reached a peak at week 5 but dropped slightly at week 7. In the continuous group, all measurements were lower than those in the intermittent groups at all times examined. All values in intermittent group A were higher than those in intermittent group B. CONCLUSION: An intermittent loading regimen appears to be more favorable for obtaining stability than continuous loading, and a 12-hour/12-hour on/off loading cycle is superior to a 24-hour/24-hour on/off protocol in promoting bone-implant contact.

Coculture with endothelial cells enhances osteogenic differentiation of periodontal ligament stem cells via cyclooxygenase-2/prostaglandin E2/vascular endothelial growth factor signaling under hypoxia.

BACKGROUND: During periodontitis and orthodontic tooth movement, periodontal vasculature is severely impaired, leading to a hypoxic microenvironment of periodontal cells. However, the impact of hypoxia on periodontal cells is poorly defined. The present study investigates responses of cocultured endothelial cells (ECs) and periodontal ligament stem cells (PDLSCs) to hypoxia. METHODS: Osteogenic differentiation, molecular characterization, and various behaviors of PDLSCs and human umbilical venous ECs under hypoxia were assessed by quantitative real-time reverse-transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. Moreover, the effect of ECs on PDLSC osteogenic differentiation was tested using NS398 (cyclooxygenase 2 blocker), SU5416 (vascular endothelial growth factor [VEGF] receptor inhibitor), AH6809, L-798106, and L-161982 (EP1/2/3/4 antagonists). RESULTS: First, hypoxia promoted osteogenic differentiation in PDLSCs and enhanced EC migration, whereas PD98059 (extracellular signal-regulated protein kinase [ERK] inhibitor) blocked, and cocultured ECs further enhanced, hypoxia-induced osteogenic differentiation. Second, NS398 impaired EC migration and prostaglandin E2 (PGE2)/VEGF release, whereas cocultured PDLSCs and exogenous PGE2 partially reversed it. Third, NS398 (pretreated ECs) decreased PGE2/VEGF concentrations. NS398-treated ECs and AH6809/SU5416-treated PDLSCs impaired cocultured EC-induced enhancement of PDLSC osteogenic differentiation. CONCLUSIONS: Hypoxia enhances ERK-mediated osteogenic differentiation in PDLSCs. Coculture with EC further augments PDLSC osteogenic differentiation via cyclooxygenase-2/PGE2/VEGF signaling.

The osteogenic differentiation of PDLSCs is mediated through MEK/ERK and p38 MAPK signalling under hypoxia.

PURPOSE: During orthodontic treatment and chronic periodontitis, the periodontal vasculature is severely impaired by overloaded mechanical force or chronic inflammation. This leads to the hypoxic milieu of the periodontal stem cell niche and ultimately affects periodontal tissue remodelling. However, the role of hypoxia in the regulation of periodontal ligament stem cell (PDLSC) behaviours still remains to be elucidated. The present study was aimed at investigating the effects of hypoxia on osteogenic differentiation, mineralisation and paracrine release of PDLSCs and further demonstrating the involvement of mitogen-activated protein kinase (MAPK) signalling in the process. METHODS: First, PDLSCs were isolated and characterised. Second, the effects of different periods of hypoxia on PDLSC osteogenic potential, mineralisation and paracrine release were investigated. Third, extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 kinase activities under hypoxia were measured. Finally, specific MAPK inhibitors PD98059 and SB203580 were employed to investigate the involvement of two kinases in PDLSC osteogenesis under hypoxia. RESULTS: Immunocytochemical staining and multilineage differentiation assays verified that the isolated cells were PDLSCs. Cell viability, alkaline phosphatase (ALP) activity, messenger RNA (mRNA) and protein levels of runt-related transcription factor 2 (Runx2) and Sp7, mineralisation and prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) release were significantly increased by hypoxia. ERK1/2 and p38 were activated in different ways under hypoxia. Furthermore, hypoxia-stimulated transcription and expression of the above-mentioned osteogenic regulators were also reversed by PD98059 and SB203580 to different degrees. CONCLUSIONS: Exposure of PDLSCs to hypoxia affected their osteogenic potential, mineralisation and paracrine release, and the process involved mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) and p38 MAPK signalling.

Analysis of time-course gene expression profiles of a periodontal ligament tissue model under compression.

OBJECTIVE: We recently reported establishment of a periodontal ligament (PDL) tissue model, which may mimic the biological behaviour of human PDL under static compression in orthodontic tooth movement (OTM). In the present study, we aimed at investigating the time-course gene expression profiles of the PDL tissue model under compression. DESIGN: The PDL tissue model was established through 3-D-culturing human PDL cells (PDLCs) in a thin sheet of porous poly lactic-co-glycolic acid (PLGA) scaffolds, which was subjected to 25g/cm(2) static compression for 6, 24 and 72h respectively. After that, its gene expression profiles were investigated using microarray assay, followed by signalling pathway and gene ontology (GO) analysis. Real-time RT-PCR verification was done for 15 identified genes of interest. The cell proliferation alteration was detected through EdU labelling. RESULTS: (1) Among the genes identified as differentially expressed, there were numerous osteoclastogenesis inducers (including CCL20, COX-1, COX-2, RANKL, PTHrP, IL-11, IL-8, etc.), osteoclastogenesis inhibitors (including IL-1Ra, NOG, OPG, etc.), and other potential bone remodelling regulators (including STC1, CYR61, FOS, etc.). (2) According to analysis of the microarray data, the most significant pathways included Cytokine-cytokine receptor interaction (containing CCL20, RANKL, IL-11, IL-8, etc.), MAPK (containing FGF7, FOS, MAP3K8, JUN, etc.) and Cell cycle (containing CDK1, CCNA2, etc.); the most significant GOs included Cell-cell signalling (containing CCL20, STC1, FGF7, PTHrP, IL-11, IL-8, etc.), Extracellular space (containing CCL20, IL-1Ra, NOG, PTHrP, IL-11, IL-8, etc.) and Microtubule-based movement (containing KIF11, KIF23, etc.). (3) After prolonged compression, cell proliferation was significantly inhibited. CONCLUSION: The present findings have expanded our understandings to the roles that PDL plays under static compression in OTM.

Effect of placement angle on the stability of loaded titanium microscrews in beagle jaws.

OBJECTIVE: To evaluate the effect of insertion angle on stability of loaded titanium microscrews in beagle jaws. MATERIALS AND METHODS: Forty-eight microscrews were inserted at four different angles (30°, 50°, 70°, and 90°) into the intraradicular zones of the mandibular first molars and third premolars of 12 beagles and immediately loaded with a force of 2 N for 8 weeks. Microcomputed tomography (micro-CT) and biomechanical pull-out tests were used to assess osseointegration of the interface. RESULTS: All micro-CT parameters and maximum pull-out force (FMAX) of the microscrews were affected by insertion angles of microscrews. Higher micro-CT parameters and FMAX were seen for implants inserted at angles between 50° and 70° (P < .05). Excessive oblique and vertical insertion angles resulted in reduced stability (P < .05). CONCLUSION: An insertion angle of 50° to 70° is more favorable than excessive oblique or vertical angles to achieve stability of microscrews.